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辅助性罗红霉素治疗对环孢素A所致牙龈增生患者龈沟液中白细胞介素-1β、转化生长因子-β1及血管内皮生长因子的影响

Effect of adjunctive roxithromycin therapy on interleukin-1β, transforming growth factor-β1 and vascular endothelial growth factor in gingival crevicular fluid of cyclosporine A-treated patients with gingival overgrowth.

作者信息

Gong Y, Lu J, Ding X, Yu Y

机构信息

Department of Stomatology, Zhongshan Hospital, Fudan University, Shanghai, China.

出版信息

J Periodontal Res. 2014 Aug;49(4):448-57. doi: 10.1111/jre.12123. Epub 2013 Aug 16.

DOI:10.1111/jre.12123
PMID:23947915
Abstract

BACKGROUND AND OBJECTIVE

Systemic macrolide antibiotic administration has been shown to result in the elimination or reduction cyclosporine A-induced gingival overgrowth. Roxithromycin (ROX) is known to have anti-inflammatory, immunomodulatory and tissue reparative effects. This study was to evaluate the effect of adjunctive ROX therapy on cyclosporine A-induced gingival overgrowth and interleukin (IL)-1β, transforming growth factor (TGF)-β1 and vascular endothelial growth factor (VEGF) levels in gingival crevicular fluid of renal transplant patients.

MATERIAL AND METHODS

Thirty-one patients with clinically significant overgrowth and 16 periodontally healthy subjects were included in this randomized, double-blind, placebo-controlled, parallel-arm study. Patients received scaling and root planing (SRP) at baseline and randomized to take either ROX or placebo for 5 d. The clinical parameters, including plaque index, papillary bleeding index, probing depth and gingival overgrowth scores, were recorded. The amounts of IL-1β, TGF-β1 and VEGF in gingival crevicular fluid were detected by ELISA. Periodontal parameters as well as gingival crevicular fluid biomarker levels were evaluated at baseline and at 1 and 4 wk post-therapy.

RESULTS

Following SRP plus ROX and SRP plus placebo therapy, significant improvements in clinical periodontal parameters of both study groups were observed (p < 0.025). In the ROX group, adjunctive ROX therapy resulted in a greater gingival overgrowth scores reduction compared with those in the placebo group at 4 wk (p < 0.017). Initial amounts of IL-1β, TGF-β1 and VEGF for both the ROX and placebo groups were significantly higher than those for healthy subjects (p < 0.017), with no statistical difference between the two study groups. At 1 and 4 wk post-therapy, significant decreases in the amounts of IL-1β, TGF-β1 and VEGF were observed in both study groups when compared with baseline (p < 0.025), but there was no difference in the levels of IL-1β and VEGF between the two study groups. The amount of decrease in TGF-β1 levels for the ROX group was statistically significant compared to that for the placebo group at 4 wk after treatment (p < 0.017).

CONCLUSION

Our study indicated that combination of ROX with non-surgical therapy improves gingival overgrowth status and decreases gingival crevicular fluid TGF-β1 levels in patients with severe gingival overgrowth. The reduction of gingival crevicular fluid TGF-β1 following ROX therapy suggests an anti-inflammatory/immunomodulatory effect of ROX on the treatment of cyclosporine A-induced gingival overgrowth.

摘要

背景与目的

已证明全身性大环内酯类抗生素给药可导致环孢素A诱导的牙龈增生消除或减轻。已知罗红霉素(ROX)具有抗炎、免疫调节和组织修复作用。本研究旨在评估辅助使用ROX治疗对肾移植患者环孢素A诱导的牙龈增生以及龈沟液中白细胞介素(IL)-1β、转化生长因子(TGF)-β1和血管内皮生长因子(VEGF)水平的影响。

材料与方法

本随机、双盲、安慰剂对照、平行组研究纳入了31例有临床显著增生的患者和16例牙周健康受试者。患者在基线时接受龈上洁治和根面平整(SRP),并随机分为服用ROX或安慰剂5天。记录临床参数,包括菌斑指数、龈乳头出血指数、探诊深度和牙龈增生评分。采用酶联免疫吸附测定法(ELISA)检测龈沟液中IL-1β、TGF-β1和VEGF的含量。在基线以及治疗后1周和4周评估牙周参数以及龈沟液生物标志物水平。

结果

在SRP加ROX和SRP加安慰剂治疗后,两个研究组的临床牙周参数均有显著改善(p < 0.025)。在ROX组,辅助使用ROX治疗在4周时导致牙龈增生评分的降低幅度大于安慰剂组(p < 0.017)。ROX组和安慰剂组的IL-1β、TGF-β1和VEGF初始含量均显著高于健康受试者(p < 0.017),两个研究组之间无统计学差异。与基线相比,治疗后1周和4周时,两个研究组的IL-1β、TGF-β1和VEGF含量均显著降低(p < 0.025),但两个研究组之间的IL-1β和VEGF水平无差异。治疗后4周,ROX组TGF-β1水平的降低量与安慰剂组相比具有统计学意义(p < 0.017)。

结论

我们的研究表明,ROX与非手术治疗联合可改善重度牙龈增生患者的牙龈增生状况,并降低龈沟液中TGF-β1水平。ROX治疗后龈沟液中TGF-β1的降低表明ROX对环孢素A诱导的牙龈增生治疗具有抗炎/免疫调节作用。

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